The immune system is a complex network of cellular and humoral components that act in concert to recognize foreign and potentially dangerous substances in the body and eliminate them in a highly targeted and controlled fashion. It can generally be divided into the innate and adaptive immune systems. The innate immune system is germline encoded and is designed to respond to conserved motifs present on pathogens. The adaptive immune system develops its antigen specificity repertoire through controlled somatic recombination processes and can respond with exquisite specificity to a wide variety of antigen types. Stimulating innate and adaptive immune responses have been shown to be an effective strategy to treat or prevent a wide variety of diseases in animals, animal disease models, and humans.
The success of immunomodulatory approaches in treating or preventing a variety of infectious diseases has been extraordinary. Despite this, there are potentially many more diseases that could be addressed using an immunotherapy approach. Two critical limitations remain: (1) properly priming innate immune cells with the right signals delivered at the optimal time and in optimal ratios to safely boost their function while also providing a suitable environment for inducing an adaptive immune response, and (2) identifying the right antigen or combination of antigens that should be targeted by the adaptive response.
Current approaches for stimulating an immune response largely depend on mixtures of compounds that are known to be immunomodulatory in isolation. At present, compounds that are used in the clinic are bulk mixtures of immune stimulants, optionally combined with antigens, which have been empirically determined to induce innate and adaptive immune responses, respectively. Despite almost a century of development, conventional approaches have yielded only two FDA approved immune stimulants: (1) alum, which is a combination of aluminum salts, and (2) monophosphoryl lipid A. While alum in particular has an impressive track record of safety and efficacy in infectious diseases, it is becoming increasingly clear that these agents do not appear sufficient to induce effective immune responses to combat more complex diseases, such as intracellular pathogens, cancer, allergies, and allergic diseases, among others. Efforts to develop new immunostimulants have largely been unsuccessful, primarily due to lack of efficacy or due to safety concerns.
The immune system evolved over millennia to respond to pathogens such as bacteria, viruses, fungi, and helminths. Consequently, most immune cells are optimized to recognize, phagocytose, process, and then respond to motifs present on microorganisms and have receptors that are “tuned” to the ratios typically present on these organisms.